The major goals of this investigation include the determination of the effects of a neonatal cure of osteopetrosis on tooth eruption and the determination of the fate of radioactively labeled donor cells during the recovery from osteopetrosis. Neonatal cure of osteopetrosis will be accomplished in newborn rats whose genotype has been determined radiographically after hypothermic anesthesia. Spleen cells from normal donors will be injected into ia littermates after whole-body radiation and the effects on eruption of incisors and first molars noted by inspection and histologically. If the teeth do not erupt, we shall attempt to accelerate osteoclastic differentiation and bone resorption by injection of parathyroid extract and vitamin D in doses that promote bone resorption. The same sequence will be repeated in animals that are not irradiated, to determine if radiation is required for the neonatal cure as it is for older rats. If the transplanted cells are not rejected in the newborn and result in a cure, this procedure will be useful in future studies on the origin of osteoclasts. The possibility that cells from normal rats cure the disease by transforming into competent osteoclasts will be investigated. We shall labor donor cells in vivo by injection of 3H-thymidine at 8-hour intervals for 3 or 4 days. This should label all dividing cells in the thymus or spleen, from which the mononuclear cells will be isolated by density gradient centrifugation. The fate of these labeled cells will be followed autoradiographically in a mutant host whose osteoclasts are developing ruffled borders and resorbing bone. Appropriate timing of the interval after cell injection should permit observation of labeled nuclei in ia osteoclasts if the cure is mediated by direct transformation of donor cells into osteoclasts.